Phase1 Study of GR121167, Single and Multiple Dose Study in Healthy Japanese Males

Inclusion criteria

• Healthy as defined as being free from clinically significant illness or disease as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital sign, laboratory tests and ECG.
• Japanese healthy male between 20 and 55 years of age inclusive, at the time of signing the informed consent.
• Body weight >= 50.0 kg and BMI within the range 18.5<= - <25.0 kg/m2 (inclusive).
• A creatinine clearance >= 80ml/min as determined by Cockcroft-Gault equation:CLcr (mL/min) = (140 - age) * Wt / (72 * Scr). Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dl. [Cockcroft, 1976]
• Non-smoker or ex-smoker having ceased smoking for at least 6 months.
• AST, ALT, alkaline phosphatase and total bilirubin =< ULN at screening.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion criteria

• A positive test for syphilis, Hepatitis B surface antigen or positive Hepatitis C antibody, HIV antigen /antibody, HTLV-1 at screening
• A positive pre-study drug screen at screening.
• History of regular alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 350 mL of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening.
• The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months preceding the first dose of study medication of this study
• The subject planned to concurrently participate in another clinical study or post-marketing study.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy excluding pollen allergy without current symptoms.
• Where participation in the study would result in donation of blood or blood products in excess of 400 mL within 4 month or 200 mL within 2 months.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Consumption of red wine, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Single QTcB >= 450 msec; at screening
• Subjects with ECG results considered clinically significant by the investigator.
• Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes or additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia).
• Subjects with a family history of sudden cardiac death.
• Subjects with a supine systolic blood pressure <90mmHg or >140mmHg and/or a supine diastolic blood pressure <55mmHg or >90mmHg and/or systolic blood pressure drop from supine to standing of >30mmHg.
• History of renal failure or renal dysfunction